Parker Waichman LLP Injury Alerts
PRESCRIPTION DRUGS (PART II): IS THE CURE WORSE THAN THE DISEASE?Jul 1, 2000
Last month we offered an examination of the pharmaceutical industry from the perspective of why the current system of drug development, approval and marketing in the United States is far from ideal. This month, we would like to delve a bit deeper into the world of prescription drugs in an effort to analyze two particularly troubling areas of scientific and public concern. The first is the problem of "over medicating" or "over prescribing." The second is the use of questionable marketing techniques or strategies by the pharmaceutical industry. We will also begin an ongoing analysis of various drugs in terms of their serious side effects or dangerous interactions, as the subject of possible litigation, or in terms of the questionable manner in which they are being marketed.
The Problem of Over-Medicating.
In "War of the Worlds, " an invincible invasion force of Martians is well on its way to the conquest of Earth when it is stopped dead in its tracks by an unseen army of bacteria that humans had been exposed to for generations. As the Martians' great war machines crashed to the ground, their crews died from diseases to which humans had long since become immune. Ironically, less than a century after H.G. Wells wrote his science fiction masterpiece, it is the human race, and not invading aliens, that finds itself increasingly more defenseless before the very same microscopic horde of bacteria, viruses and toxins. The truth, indeed, is stranger than fiction.
How is it that a species like man, which is at the height of its scientific prowess, is, at the very same time, in mortal danger from such an unlikely source? Consider the following:
The-overuse and misuse of antimicrobial agents (antibiotics, antimalarials, soaps and cleansers) have accelerated the natural process by which microbes become resistant to such agents. In poor countries where people cannot afford a complete course of drug therapy or must settle for weaker or cheaper drugs, only the more susceptible microbes are killed off. This "underuse" allows the more resistant forms of the microbes to survive and dominate.
In wealthier countries the "overuse" of anti-microbials is even more problematic. For example, people continue to insist upon using antibiotics to "fight" viral infections such as colds. Since such infections are not bacterial, antibiotics are useless against them. Each similar misuse of antibiotics does nothing more than allow bacteria another opportunity to build up its resistance. It is estimated by the Centers for Disease Control and Prevention that a full one-third of the antibiotics taken by Americans on an outpatient basis are unnecessary.
The extensive use of antibiotics for livestock and poultry has also led to more resistant microbes which pose a direct threat to humans. Numerous anti-malarial drugs are no longer effective in large areas of the world. The same is true for standard treatments for gonorrhea and tuberculosis. Antibacterial soaps, lotions and other household products have added to the problem since their widespread use simply eliminates the weakest bacteria and, it is suspected, hastens the evolutionary process by which bacteria develop resistance against antimicrobial agents. In June of this year, the American Medical Association urged the government to strengthen regulations concerning such household products.
Dr. Stuart Levy, Director of the Center for Adaptation and Drug Resistance at Tufts University, also expressed his concerns at a press briefing on infectious diseases held by the A.M.A. on June 1, 2000. Dr. Levy urged consumers to buy only products without antibacterials and manufacturers to go back to making plain, old-fashioned soap and detergent. The problem, as Dr. Levy sees it, is that antibacterials do not kill all bacteria. Instead, they simply aid in "survival of the fittest," thereby leaving only the strongest bacteria to survive and multiply.
Dr. Levy's research discloses that bacteria resistant to antibacterials are likewise resistant to various antibiotics. Thus, the extensive use of these household products may be contributing to the increase in infections that are difficult or impossible to treat. As the World Health Organization (WHO) report of June 12, 2000 entitled "Overcoming Antimicrobial Resistance" recognizes, the major infectious diseases are gradually becoming impervious to existing drugs, reducing the curative power of "once life-saving medicines to that of a sugar pill."
Thus, we have reached the point where the very quest for an environment free of "super" germs has become the vehicle by which those dangerous microbials have gained the upper hand. In order to avoid the same catastrophic fate as the fictional aliens in "War of the Worlds, " we now must develop entirely new families of even more powerful antibiotics while, if possible, re-establishing the natural balance between ourselves and the unseen primitive world we have tried so hard to eradicate with our advanced scientific knowledge.
The Business of Marketing Drugs: Is it a recipe for disaster?
No prescription drug can be even modestly successful without the cooperation of tens of thousands of physicians. In the end, pharmaceutical companies must rely on individual physicians to write and re-write the hundreds of thousands or millions of prescriptions required to make a drug profitable. How is it that one of the world's largest industries can base its very survival on unpredictable acts of individuals over whom it has no apparent control? The answer is quite simple. The pharmaceutical companies do, in fact, control much of the medical profession in the very same way Pavlov controlled his dogs.
Promotional gifts have always been associated with American business. Every type of industry has always given away logo-laden trinkets such as pens, key chains, calendars, paperweights, letter openers, coffee mugs, flash lights and, of course, free samples. The goal of such "generosity" is no secret. It is designed to remind potential customers of a particular product or company name as often as possible. While this practice can sometimes be "tacky," it is harmless enough when associated with most products and services. Unfortunately, when it comes to the pharmaceutical industry, the gifts involved can be quite lavish and the goal can be much more subliminal.
Traditionally, pharmaceutical companies would promote goodwill and name recognition by the widespread distribution of trivial gifts to physicians and hospitals. Along with promotional information and free samples of its products, a drug company would hand out pens, pads, paperweights and the like through its sales representatives.
Although these marketing techniques were unquestionably designed to aid in the sale of pharmaceutical products in some tangible, if not measurable, way, there never seemed to be any overt manipulative or coercive aspect to the practice.
In the early 1980s, however, changes in the pharmaceutical industry apparently convinced drug manufacturers that they needed to have more control over the physicians who determined which drugs were prescribed to the public. Higher research and development costs, greater financial risks from litigation and unsuccessful products, increased competition, and the enormous profit potential for "breakthrough" type drugs for HIV/AIDS, cancer, diabetes, obesity and other contemporary medical problems seem to have made drug companies less willing to leave the most critical aspect of the pharmaceutical marketing cycle to chance. Thus, the industry as a whole began to bombard the medical profession with an array of lavish gifts and funding. This has raised serious questions as to conflicts of interest, medical ethics, manipulation and other potential abuses which strongly suggest prescriptions are now very often written as a direct result of the quality of the gifts associated with the drug, rather than the quality of the drug associated with the gifts.
The following is only a partial list of the kind of gifts and funding given out to members of the medical profession:
* Paid vacations;
* Airline travel miles awarded on the basis of prescriptions written;
* Complimentary meals and entertainment at Continuing Medical Education (CME) courses;
* Consultation fees;
* Financial support of CME-accredited activities;
* Sponsorship of pseudo-CME courses. (These are not accredited and are usually little more than thinly veiled advertising campaigns);
* Meals of all types ranging from buffets offered to hospital residents, to lunches and dinners at the finest restaurants for physicians and their families;
* Funding for travel or lodging;
* Sponsorship of events for physicians and their families at theme parks including meals, entertainment, and use of the facilities.
In January of this year, the Journal of the American Medical Association presented an excellent Commentary by Dr. Robert M. Tenery and Review by Dr. Ashley Wazana on this subject. (JAMA, Vol. 283, No. 3). We highly recommend both pieces, which are extensively annotated, to our readers who wish to read more about this controversial issue. We also highly recommend David D. Kirkpatrick's article entitled, "Selling Happiness" in the May 15th issue of New York Magazine. Mr. Kirkpatrick has certainly done his homework and everyone taking a relatively new prescription drug of any kind would be well served by reading this captivating expose of an industry practice that uses "free gifts, dinners, and propaganda and research funds “to” capture the minds of doctors." There can be little, if any, doubt that an industry that commands an army of 68,000 sales representatives and spends $9 billion annually on marketing to its target audience ($12,000 for each doctor in the U.S.), wants (and gets) much more than just name recognition. In fact, many suspect that the degree to which many doctors now find themselves influenced by this highly questionable practice borders on the unethical.
Dr. Robert Goodman, a New York internist fed up with this entire matter, has launched the "No Free Lunch" campaign. His T-shirts, coffee mugs and pens read "NO FREE LUNCH: JUST SAY NO TO DRUG REPS." He even has a website, www.nofreelunch.org which includes "facts and research about the influence of drug companies on medicine." Dr. Goodman openly admits that: "What really annoyed me was physicians' willingness to be bribed."
Dangerous Interactions and Side Effects.
Whenever we take a foreign substance into our bodies, there are consequences. Some of these consequences are intended, while others are not. The ones we do not want to occur may take the form of an allergic reaction or a side effect. Either of these may be very mild or extremely severe. When a combination of two or more substances is taken, an additional consequence should be anticipated as a result of the interaction between the substances themselves. While all of this sounds quite simple, we are certain that each of you has a story about an unpleasant or dangerous side effect or interaction that you or someone you know suffered.
When you consider that just four substances can be taken in 12 different combinations, imagine the mind-boggling number of combinations that can be created by mixing any number of prescription drugs, non-prescription drugs, dietary supplements, foods, beverages and skin and hair products with one another. If you are a "visual" person, just imagine the number of combinations that are possible by taking all of the products in a large drug store (remember to include all prescription and non-prescription drugs, supplements, cosmetics, shampoos, soaps, hair sprays, perfumes, toiletries, sun tan lotions, insect repellents, solvents, dyes, etc.) and then all of the products in a supermarket (like detergents, soaps, waxes, polishes, aerosol sprays, household cleaners and solvents, insecticides, pet products, all foods and beverages, etc.). Now, add all of the products in a hardware store (paints, solvents, chemicals, and lawn and garden products) and an automotive supply store (chemical sprays, waxes, polishes, and solvents). To all of this add in variables like chemical additives in foods, insecticide residue on and in fruits and vegetables, antibiotic residue in meats and poultry, chemical residue in fish and shellfish, airborne exhaust fumes and toxins from fires and pollution of drinking water from toxic waste, illegal dumping, chemical and petroleum plants and municipal landfills. Finally, don't forget the impact of alcoholic beverages. The effect that all of these products have on us when taken alone or in combination also varies depending on age, sex, race, general health, allergies, hereditary traits and environment.
Now that you have some idea of the scope of the problem, consider the following: No pharmaceutical company can even begin to compile a complete list of possible interactions between any drug and all other combinations of substances which a person might use along with it. Thus, any "list" of interactions for any prescription drug is always pitifully incomplete. At best, it is a feeble effort to warn consumers of the more obvious or best known interactions of which the manufacturer is aware.
Unfortunately, many harmful interactions are only discovered after someone actually experience one. Also, there is the tendency of people to treat interaction lists as complete. This trust is terribly misplaced. Finally, people tend to ignore the possibility that serious interactions may occur between a prescription drug and otherwise harmless non-prescription substances. Thus, they fail to read labels or discuss the potential for this particular type of interaction with their physician.
It is your responsibility to know as much as you can about the drugs and other products you are using in terms of their own potential side effects as well as known interactions. You must also be vigilant when using any drug or combination of drugs and other products. If an unusual condition occurs, you should consult a qualified medical professional immediately to determine if the condition is or may be caused by the drug or the combination of the drug and something else. You may not only save your own life but, you may also save others if your problem is the first consult a qualified medical professional immediately to determine if the condition is or may be caused by the drug or the combination of the drug and something else. You may not only save your own life but, you may also save others if your problem is the first of its kind.
The following list of interactions is but a tiny sample of drugs that can have clinically important and dangerous, even deadly, adverse reactions:
* Propulsid and Sporanox
* Tagamet and Coumadin
* Prozac and Dilantin
* Erythromycin and Halcyon
* Tagamet and Dilantin
* Lopid and Mevacor
* Calan and Duraquin
* Tagamet and Theo-Dur
* Eldepryl and Norpramine
* Calan and Lanoxin (Digoxin)
* Erythromycin and Seldane
Public Citizen reports that "most doctors are probably less informed than you are" on the subject of drug induced illnesses and prescribing practices. In fact, studies have found that: "70% of doctors treating Medicare patients flunked an exam on their knowledge of prescribing to older adults." Moreover, "48% of patients taking three or more drugs were given drugs with one or more harmful interactions with other drugs."
Recently, the Committee on Safety of Medicines (the British equivalent of our FDA) warned physicians, pharmacists and the public about several clinically important drug interactions between the popular dietary supplement St. John's Wort and prescription drugs such as indinavir (CRIXIVAN), nelfinavir (VIRACEPT), ritonavir (NORVIR), saquinavir (INVIRASE), efavirenz (SUSTIVA), nevirapine (VIRAMMUNE), warfarin (COUMADIN), citalopram (CELEXA), fluoxetine (PROZAC), fluvoxamine (LUVOX), paroxetine (PAXIL), sertraline (ZOLOFT), cyclosporine (NEORAL, SANDIMMUNE), theophylline (THEO-DUR), digoxin (LANOXIN), naratriptan (AMERGE), rizatriptan (MAXALT), sumatriptan (IMITREX), zolmitriptan (ZOMIG) and oral contraceptives.
Although the FDA was "strongly urged" by the Health Research Group of Public Citizen to issue a similar warning to American physicians and patients, they "received a predictably weak responses" from Dr. Janet Woodcock (Director of the FDA's Center for Drug Evaluation). While Dr. Woodcock clearly acknowledged the risks associated with the use of St. John's Wort in combination with certain prescription drugs, she explained that the FDA’s current strategy is to explore ways "to address risks with the use of the dietary supplement" and "how to best implement a variety of possible risk management tools to address the broad nature of the problem." According to Public Citizen, this simply means that, while the FDA drags its feet (as usual), "the public is not being warned about potentially serious drug interactions."
Since dietary supplements are exempt from any testing requirements under the Dietary Supplement Health and Education Act (DSHEA) of 1994, the American public, according to Public Citizen, has been turned into guinea pigs in a large uncontrolled experiment" where interactions "can only be detected if people are injured or killed."
Obviously, by this point you should realize that when it comes to protecting yourself from dangerous drug interactions, you are your first and best line of defense. Read all warnings carefully, do some research, ask questions of your doctor or pharmacist, don't take interaction "lists" as the final word, and note any unusual condition and bring it to the attention of your doctor immediately.
Moving on to a consideration of "side effects," there are two major concerns which we see as serious problems with today's pharmaceutical landscape. The first is the fact that the quest for "a cure for everything" coupled with a societal mind set of instant gratification has caused such a proliferation of inadequately tested new drugs that side effects are being discovered or taken seriously only after a drug is marketed. This has led to two recent phenomena, namely, drugs being voluntarily recalled or ordered removed from the market in an alarming number and warning labels that must be repeatedly updated because they lag dangerously behind. In other words, you and everyone around you have become guinea pigs in vast uncontrolled experiments with extremely dangerous drugs.
The second problem involving side effects is the marketing strategy of today's pharmaceutical companies which is to use Madison Avenue advertising campaigns to entice the public into pressuring their doctors for prescriptions for new drugs. These advertisements are extremely problematic in that they glamorize prescription drugs as the answer to the prayers of each target group while down-playing, minimizing or even misleading the public as to the drug's most dangerous side effects.
Rezulin is an example of the first problem. Clearly, this is a drug that was rushed to market in the United States with inadequate testing and despite an enormous amount of evidence that it was unsafe. The risks from the drug's potential side effects far outweighed any benefit the drug offered diabetics. Moreover, the manufacturer engaged in a shell game with the FDA by withholding test results in a way that caused the warning label to lag far behind what was really known about the side effects. This caused the need for four upgraded warning labels before the drug was removed from the market. The body count just got too high to justify any longer. Unfortunately, as in the case of Rezulin, the FDA is too often part of the problem rather than the key to the solution.
The second problem is exemplified by marketing campaigns like the one for the drug DIFLUCAN (fluconazole) tablets. Its benefits do not legitimately outweigh the enormous risks to its chosen target market. DIFLUCAN is the first of a new subclass of synthetic triazole antifungal agents marketed by Pfizer, Inc. In short, the drug is designed to treat serious fungal infections. The advertising being carried on television, however, specifically targets women who are encouraged to use the drug instead of creams and ointments to treat yeast infections.
Granted, yeast infections can be painful, embarrassing and extremely uncomfortable, yet is any of that serious enough to risk the following published dangers:
DIFLUCAN has been associated with rare cases of serious hepatic (liver) toxicity, including fatalities. This danger bears no obvious dangers:
* DIFLUCAN has been associated with rare cases of serious hepatic (liver) toxicity, including fatalities. This danger bears no obvious relationship to total daily dose, duration of therapy, sex or age of patient.
* Anaphylaxis (allergic reaction) in rare cases.
* Exfoliative skin disorders (detachment and shedding of skin) in rare cases. In patients with serious underlying diseases, these disorders can be fatal in rare cases.
* Kidney problems ranging from mild to failure to death.
* A 26% incidence of drug related adverse events as opposed to only 16% for intravaginal agents.
* Clinically or potentially significant drug interactions between DIFLUCAN and the following have been observed: Oral hypoglycemics (ex. glyburide), Coumarin-type anticoagulants, Phenytoin, Cyclosporine, Rifampin, Theophylline, Terfenadine, Cisapride, Astemizole, Rifabutin, and Tacrolimus. These interactions may cause reactions such as death, kidney impairment, blood disorders or chemical imbalance, serious cardiac dysrhythmias, cardiac "events", nephrotoxicity as well as other, yet unknown, reactions.
* (Based on pregnant animal testing) - Impairment of material weight gain, abortion, increased placental weights, fetal abnormalities.
* Although there are no adequate and well controlled studies in pregnant women, there have been reports of multiple congenital abnormalities in infants whose mothers were treated for three (3) or more months with high dosages of DIFLUCAN. Thus, DIFLUCAN should only be used in pregnancy "if the potential benefit justifies the possible risk to the fetus."
* Nausea, vomiting.
* Abdominal pain.
* Skin rash.
* Not recommended for use by nursing mothers.
* Seizures, Stevens-Johnson syndrome, alopecia, blood and metabolic disorders have occurred "under conditions where a causal association is uncertain."
To be sure, this drug may be quite beneficial to treat some people (men, women and children) for some very serious conditions. That, however, would be a very small market for this drug. One has to wonder, however, why Pfizer has specifically chosen women with yeast infections exclusively as its target market on national television. Could it be because that is precisely where Pfizer knows its biggest potential market is?
Obviously, a simple pill is much more attractive as a treatment than "messy" creams which need to be applied internally (as the commercials point out). If you know about the drug and then listen to the commercials, however, you will immediately notice that it is the mildest side effects which are emphasized. Serious side effects are barely mentioned and even the dramatically higher "incidence of drug related adverse reactions" (61% higher than for intravaginal agents) is glossed over without any mention of the actual figures.So, if you are a woman and have a yeast infection, you ought to think twice before opting for convenience over safety.
Unfortunately, physicians all over the country have also fallen for the hype (and the dinners, and the gifts, and the free samples, etc., etc., etc.). They are prescribing the drug at a brisk rate and handing out free samples to their female patients as if DIFLUCAN is as safe as jelly beans. Clearly, it is not.
Thus, between interactions that are largely a matter of trial and error and side effects which are often cleverly concealed or minimized, drugs without proven track records should not be regarded as safe. In fact, Public Citizen now advocates a Seven-Year-Rule stating:
"You should wait at least seven years from the date of release to take any new drug unless it is one of the those rare ‘breakthrough’ drugs that offers you a documented therapeutic advantage over older proven drugs. New drugs are tested in a relatively small number of people before being approved, and serious adverse effects or life-threatening drug interactions may not be detected until the new drug has been taken by hundreds of thousands of people. A number of new drugs have been withdrawn within their first five years after approval. Also, serious new adverse reaction warnings have been added to the labeling of a number of drugs, or new interactions have been detected, usually within the first five years after a drug's release."
We certainly agree with this position.